US 12,365,722 B2
Multispecific antibodies targeting multiple epitopes on the HIV-1 envelope
Yuxing Li, Boyds, MD (US); James Steinhardt, Westminster, MD (US); Javier Guenaga, San Diego, CA (US); John R. Mascola, Rockville, MD (US); Tae-Wook Chun, North Bethesda, MD (US); Susan Moir, Washington, DC (US); and Chi-I Chiang, Rockville, MD (US)
Assigned to University of Maryland, College Park, College Park, MD (US); University of Maryland, Baltimore, Baltimore, MD (US); The United States of America, as Represented by the Secretary, Department of Health and Human Servives, Bethesda, MD (US); and International AIDS Vaccine Initiative, New York, NY (US)
Appl. No. 17/285,956
Filed by University of Maryland, College Park, College Park, MD (US); University of Maryland, Baltimore, Baltimore, MD (US); The United States of America, as Represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); and International AIDS Vaccine Initiative, New York, NY (US)
PCT Filed Oct. 18, 2019, PCT No. PCT/US2019/057089
§ 371(c)(1), (2) Date Apr. 16, 2021,
PCT Pub. No. WO2020/082045, PCT Pub. Date Apr. 23, 2020.
Claims priority of provisional application 62/749,510, filed on Oct. 23, 2018.
Claims priority of provisional application 62/748,228, filed on Oct. 19, 2018.
Prior Publication US 2022/0227845 A1, Jul. 21, 2022
Int. Cl. C07K 16/10 (2006.01); A61K 39/42 (2006.01); A61K 45/06 (2006.01); A61P 31/18 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/1063 (2013.01) [A61K 39/42 (2013.01); A61K 45/06 (2013.01); A61P 31/18 (2018.01); C07K 16/1045 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 30 Claims
OG exemplary drawing
 
1. A multispecific anti-HIV antibody that binds to multiple epitopes on HIV envelope protein, wherein the antibody comprises
i. amino acid sequences that bind to a V1/V2 apex glycan epitope selected from the group consisting of:
(a) an amino acid sequence comprising a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises QFRFDGYG (SEQ ID NO: 2), CDR H2 comprises ISHDGIKK (SEQ ID NO: 3) and CDR H3 comprises AKDLREDECEEWWSDDFGKQLPCAKSRGGLVGIADN (SEQ ID NO: 4); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR LI comprises TSNIGNNF (SEQ ID NO: 6), CDR L2 comprises ETD (SEQ ID NO:7) and CDR L3 comprises ATWAASLSSARV (SEQ ID NO: 8); and
(b) an amino acid sequence comprising a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GNTLKTYD SEQ ID NO: 10), CDR H2 comprises ISHEGDKK (SEQ ID NO: 11) and CDR H3 comprises AKGSKHRLRDYALDDDGALNWAVDVDYLSNLEF (SEQ ID NO: 12); and
an amino acid sequence comprising a CDR LI, CDR L2 and CDR L3, wherein CDR LI comprises HSLIHGDRNNY (SEQ ID NO: 14), CDR L2 comprises LAS (SEQ ID NO: 15) and CDR L3 comprises MQGRESPWT (SEQ ID NO: 16);
ii. an amino acid sequence that binds to a V3-base glycan region epitope, wherein the amino acid comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GASISDSY (SEQ ID NO: 18), CDR H2 comprises VHKSGDT (SEQ ID NO:19) and CDR H3 comprises ARTLHGRRIYGIVAFNEWFTYFYMDV (SEQ ID NO: 20); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises SLGSRA (SEQ ID NO: 22), CDR L2 comprises NNQ (SEQ ID NO: 23) and CDR L3 comprises HIWDSRVPTKWV (SEQ ID NO: 24);
iii. an amino acid sequence that binds to a CD4 binding site (CD4bs) epitope wherein the amino acid comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GYTFTAHI (SEQ ID NO: 26), CDR H2 comprises IKPQYGAV (SEQ ID NO: 27) and CDR H3 comprises AR (SEQ ID NO: 28); and an amino acid sequence comprising a CDR LI, CDR L2 and CDR L3, wherein CDR LI comprises QGVGSD (SEQ ID NO: 30), CDR L2 comprises HTS (SEQ ID NO: 31) and CDR L3 comprises QVLQF (SEQ ID NO: 32);
iv. an amino acid sequence that binds to a gp120/gp41 interface epitope wherein the amino acid sequence comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GYRFNFYH (SEQ ID NO: 34), CDR H2 comprises ISPYSGDK (SEQ ID NO: 35) and CDR H3 comprises DDTGTYFCAKGLLRDGSSTWLPYL (SEQ ID NO: 36); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises NSVCCSHKS (SEQ ID NO: 38), CDR L2 comprises EDN (SEQ ID NO: 39) and CDR L3 comprises CSYTHNSGCV (SEQ ID NO: 40); and
v. an amino acid sequence that binds to a membrane proximal external region (MPER) epitope wherein the amino acid sequence comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GFDFDNAW (SEQ ID NO: 42), CDR H2 comprises ITGPGEGWSV (SEQ ID NO: 43) and CDR H3 comprises TGYYFCARTGKYYDFWSGYPPGEEYFQD (SEQ ID NO: 44); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises RGDSLRSHYAS (SEQ ID NO: 46), CDR L2 comprises GKNNRPS (SEQ ID NO: 47) and CDR L3 comprises SSRDKSGSRLSV (SEQ ID NO: 48).